Modified Citrus Pectin Alleviates Diabetic Kidney Disease by Suppressing Pyroptosis in Renal Tubular Epithelial Cells via the Cx43‐ERK1/2 Signaling Pathway

Modified citrus pectin (MCP) exhibits antioxidant properties, while persistent oxidative stress is one of the key mechanisms contributing to the progression of diabetic kidney disease (DKD). However, its role and underlying mechanisms in the progression of DKD remain inadequately understood. The objective is to clarify the functions of MCP in the regulation of renal tubular epithelial cell injury and to substantiate the underlying mechanisms. For in vivo experiments, C57BL/6J mice and db/db mice were used to verify the role of MCP. Normal rat renal tubular epithelial cells (NRK-52E) and Connexin 43 (Cx43^+/-) NRK-52E were used to investigate the mechanism of MCP in in vitro. MCP ameliorated serum creatinine, urine protein, and renal interstitial damage in db/db mice, inhibited the expression of P-extracellular signal-regulated kinase (P-ERK) and Gasdermin D-NT（GSDMD-NT） proteins in renal tissue and improved the changes in indicators such as reactive oxygen species(ROS)/ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msubsup><mml:mi>O</mml:mi> <mml:mn>2</mml:mn> <mml:mo>-</mml:mo></mml:msubsup> <mml:annotation>${\rm O_{2}^{-}}$</mml:annotation></mml:semantics> </mml:math> , P-ERK, thioredoxin-interacting protein(Txnip), thioredoxin 1（Trx1）, and Cx43 induced by Px12. MCP inhibited renal tubular epithelial cells pyroptosis via the Cx43-ERK1/2 signaling pathway.